Satiety inducing composition comprising Neuropeptide Y analogues and methods of inducing satiety and treating a disease or condition associated with it

ABSTRACT

Satiety inducing composition comprises Neuropeptide Y analogues which are effective for inducing satiety and for treating diseases and conditions associated with a lacking of, or having lowered, satiety.

PRIOR PATENT APPLICATIONS

This is a divisional application of U.S. patent application Ser. No.08/422,839, filed Apr. 17, 1995, by the same inventors, and now U.S.Pat. No. 6,075,009.

This invention was made with Government support under Grant No. RO1CA47217-06 from the National Cancer Institute. The Government may havecertain rights in this invention.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention concerns novel Neuropeptide Y analogs,pharmaceutical formulations containing the same and methods of loweringblood pressure and inducing satiety in a subject employing the same.

2. Description of the Background

Neuropeptide Y is a 36 amino acid member of the pancreated polypeptidefamily. It is highly concentrated in both the central and peripheralmammalian nervous system. It apparently serves important functions inthe control of blood pressure, satiety, and other responses. The aminoacid sequence of Neuropeptide Y is known. See, e.g., K. Tatemoto, Proc.Natl. Acad. Sci. USA 79, 5485-5489 (1982).

Neuropeptide Y analogs are disclosed in U.S. Pat. No. 5,026,685 toBoublik et al. The compounds are indicated to be active in lowering theblood pressure of mammalian subjects. The compounds are indicated to be18-20 amino acids in length, and include amino acid residues 19 to 36 ofhuman NPY (see, e.g., Column 2, lines 25-35 therein). AdditionalNeuropeptide Y analogs are disclosed in U.S. Pat. No. 5,328,899 toBoublik et al.

A recent study proposed two modified fragments of NPY, called PYX₁ andPYX₂, to be specific NPY receptor antagonists. Both compounds areanalogs of the 27-36 residue C-terminal fragment. Both compounds have aD-amino acid substitution at Thr³². [3-(2,6-dichlorobenzyl)] issubstituted at Tyr²⁷ on PYX₁, and is substituted at both Tyr²⁷ and Tyr³⁶in PYX₂. See K. Tatemoto, Ann. NY Acad. Sci. 611, 1-6 (1990); K.Tatemoto et al., Proc. Natl. Acad. Sci. USA 89, 1174-1178 (1992).

SUMMARY OF THE INVENTION

The present invention is based on the a new group of Neuropeptide Yanalogs. Active Neuropeptide Y (NPY) analogs. The compounds preferablyinclude amino acids 28-35 of human NPY, and include a D-Thr amino acidsubstitution at the Thr³² position.

The present invention relates to a method of lowering blood pressure ina subject in need of such treatment by administering to the subject theactive compounds given above in an amount effective to lower bloodpressure.

The present invention relates to a method of inducing satiety in asubject in need of such treatment by administering to the subject theactive compounds given above in an amount effective to induce satiety.

The present invention relates to a pharmaceutical formulation comprisingthe active compounds given above in combination with a pharmaceuticallyacceptable carrier. The active compound maybe included in theformulation in a pharmaceutically effective amount i.e., an amounteffective to lower blood pressure; an amount effective to inducesatiety.

The invention also applies the active compounds given above to thepreparation of a medicament for lowering blood pressure in a mammaliansubject, or for inducing satiety in a mammalian subject.

The foregoing and other objects and aspects of the present invention areexplained in detail in the specification set forth hereinbelow.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The amino acid sequences disclosed herein are presented in the amino tocarboxy direction, from left to right. Where the amino acid residue hasisomeric forms, it is the L-form of the amino acid that is represented,unless otherwise indicated.

The methods of the present invention are concerned primarily with thetreatment of human subjects, but may also be employed for the treatmentof other mammalian subjects, such as dogs, cats and cows, for veterinarypurposes. Subjects may be those subjects in need of such treatment forany reason for which lowering of blood pressure would be of therapeuticbenefit, including but not limited to those subjects afflicted withhypertension or high blood pressure.

The active compounds of the present invention are, in general, NPYanalogs that are NPY fragments. The compounds preferably include aminoacids 28-35 of NPY, and include a D-Thr amino acid substitution at theThr³² position. The compounds are preferably at least 8, 9 or 10 aminoacids in length, and are preferably not more than 15, 16, 17 or 18 aminoacids in-length.

Specific examples of active compounds of the present invention are asfollows:

 I: D-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH₂  (SEQ ID NO:1);

I^(Ac): Ac-D-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH₂  (SEQ IDNO:2);

IIB:D-Asp-Pro-Lys-Ser-Pro-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH₂  (SEQID NO:3);

IIB^(Ac):Ac-D-Asp-Pro-Lys-Ser-Pro-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH₂  (SEQID NO:4);

III: D-Phe(NO₂)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(NO₂)-NH₂  (SEQID NO:5);

III^(Ac):Ac-D-Phe(NO₂)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(NO₂)-NH₂  (SEQ IDNO:6);

IV: D-Phe(pF)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pF)-NH₂  (SEQ IDNO:7);

IV^(Ac):Ac-D-Phe(pF)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pF)-NH₂  (SEQ IDNO:8);

V: D-Phe(pCl)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pCl)-NH₂  (SEQ IDNO:9);

V^(Ac):Ac-D-Phe(pCl)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pCl)-NH₂  (SEQ IDNO:10);

VI: D-Phg-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phg-NH₂  (SEQ ID NO:11);

and

VI^(Ac): D-Phg-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phg-NH₂  (SEQ IDNO:12).

The terms used herein have their standard meanings. The term “Ac” meansacetyl; the term “Phe(NO₂)” refers to phenylalanine substituted by —NO₂on the phenylalanine ring, preferably at the para position, the term“Phe(pCl)” refers to phenylalanine substituted by —Cl on thephenylalanine ring at the para position, and the term “Phe(pF)” refersto phenylalanine substituted by —F on the phenylalanine ring at the paraposition.

The compounds of the invention may be prepared in accordance with knowntechniques, such as solid phase-chemistry. See, e.g., U.S. Pat. No.4,415,558 to Vale et al.

The active compounds disclosed herein may be prepared in the form oftheir pharmaceutically acceptable salts. Pharmaceutically acceptablesalts are salts that retain the desired biological activity of theparent compound and do not impart undesired toxicological effects.Examples of such salts are (a) acid addition salts formed with inorganicacids, for example hydrochloric acid, hydrobromic acid, sulfuric acid,phosphoric acid, nitric acid and the like; and salts formed with organicacids such as, for example, acetic acid, oxalic acid, tartaric acid,succinic acid, maleic acid, fumaric acid, gluconic acid, citric acid,malic acid, ascorbic acid, benzoic acid, tannic acid, palmitic acid,alginic acid, polyglutamic acid, naphthalenesulfonic acid,methanesulfonic acid, p-toluenesulfonic acid, naphthalenedisulfonicacid, polygalacturonic acid, and the like; (b) salts formed fromelemental anions such as chlorine, bromine, and iodine, and (c) saltsderived from bases, such as ammonium salts, alkali metal salts such asthose of sodium and potassium, alkaline earth metal salts such as thoseof calcium and magnesium, and salts with organic bases such asdicyclohexylamine and N-methyl-D-glucamine.

Pharmaceutical compositions for use in the present method of loweringblood pressure include those suitable for inhalation, oral, rectal,topical, (including buccal, sublingual, dermal and intraocular)parenteral (including subcutaneous, intradermal, intramuscular,intravenous and intraarticular) and transdermal administration. Thecompositions may conveniently be presented in unit dosage form and maybe prepared by any of the methods well known in the art. Theformulations may conveniently be presented in unit dosage form and maybe prepared.by any of the methods well known in the art.

The dose of active compound administered will vary according to theroute of administration, the manner of formulation, the condition of thesubject, and the dose at which adverse pharmacological effects occur.One skilled in the art will take such factors into account whendetermining dosage. In general, in one preferred embodiment, the dosagewill be from 400 or 500 up to about 1000, 2000, or 4000 nM/kg subjectbody weight.

In the manufacture of a medicament according to the invention (a“formulation”), active agents or the physiologically acceptable saltsthereof (the “active compound”) are typically admixed with, among otherthings, an acceptable carrier. The carrier must be acceptable in thesense of being compatible with any other ingredients in the formulationand must not be deleterious to the patient. The carrier may be a solidor a liquid, or both, and is preferably formulated with the compound asa unit-dose formulation, for example, a tablet, which may contain from0.5% to 99% by weight of the active compound. One or more activecompounds may be incorporated in the formulations of the invention(e.g., the formulation may contain one or more additionalanti-tubercular agents as noted above), which formulations may beprepared by any of the well known techniques of pharmacy consistingessentially of admixing the components, optionally including one or moreaccessory therapeutic ingredients.

Formulations suitable for oral administration may be presented indiscrete units, such as capsules, cachets, lozenges, or tablets, eachcontaining a predetermined amount of the active compound; as a powder orgranules; as a solution or a suspension in an aqueous or non-aqueousliquid; or as an oil-in-water or water-in-oil emulsion. Suchformulations may be prepared by any suitable method of pharmacy whichincludes the step of bringing into association the active compound and asuitable carrier (which may contain one or more accessory ingredients asnoted above). In general, the formulations of the invention are preparedby uniformly and intimately admixing the active compound with a liquidor finely divided solid carrier, or both, and then, if necessary,shaping the resulting mixture. For example, a tablet may be prepared bycompressing or molding a powder or granules containing the activecompound, optionally with one or more accessory ingredients. Compressedtablets may be prepared by compressing, in a suitable machine, thecompound in a free-flowing form, such as a powder or granules optionallymixed with a binder, lubricant, inert diluent, and/or surfaceactive/dispersing agent(s). Molded tablets may be made by molding, in asuitable machine, the powdered compound moistened with an inert liquidbinder. Formulations for oral administration may optionally includeenteric coatings known in the art to prevent degradation of theformulation in the stomach and provide release of the drug in the smallintestine.

Formulations suitable for buccal (sub-lingual) administration includelozenges comprising the active compound in a flavored base, usuallysucrose and acacia or tragacanth; and pastilles comprising the compoundin an inert base such as gelatin and glycerin or sucrose and acacia.

Formulations of the present invention suitable for parenteraladministration comprise sterile aqueous and non-aqueous injectionsolutions of the active compound, which preparations are preferablyisotonic with the blood of the intended recipient. These preparationsmay contain anti-oxidants, buffers, bacteriostats and solutes whichrender the formulation isotonic with the blood of the intendedrecipient. Aqueous and non-aqueous sterile suspensions may includesuspending agents and thickening agents. The formulations may bepresented in unit/dose or multi-dose containers, for example sealedampoules and vials, and may be stored in a freeze-dried (lyophilized)condition requiring only the addition of the sterile liquid carrier, forexample, saline or water-for-injection immediately prior to use.Extemporaneous injection solutions and suspensions may be prepared fromsterile powders, granules and tablets of the kind previously described.

Formulations suitable for rectal administration are preferably presentedas unit dose suppositories. These may be prepared by admixing the activecompound with one or more conventional solid carriers, for example,cocoa butter, and then shaping the resulting mixture.

Formulations suitable for topical application to the skin preferablytake the form of an ointment, cream, lotion, paste, gel, spray, aerosol,or oil. Carriers which may be used include vaseline, lanoline,polyethylene glycols, alcohols, transdermal enhancers, and combinationsof two or more thereof.

Formulations suitable for transdermal administration may be presented asdiscrete patches adapted to remain in intimate contact with theepidermis of the recipient for a prolonged period of time. Formulationssuitable for transdermal administration may also be delivered byiontophoresis (see, e.g., Pharmaceutical Research 3, 318 (1986)) andtypically take the form of an optionally buffered aqueous solution ofthe active compound.

The following examples are provided to more fully illustrate the presentinvention and should not be construed as restrictive thereof. In thefollowing examples, temperatures are given in degrees centigrade unlessotherwise indicated.

EXAMPLES Example 1

Synthesis of NPY27-36 (D-Tyr^(27,36), D-Thr³²)

NPY27-36 (D-Tyr^(27,36), D-Thr³²) was synthesized using Fmoc-BOPchemistry in accordance with known techniques. The automated BIOSEARCHmodel 9600 peptide synthesizer was used to produce the peptide. Theamino acid derivatives were Arg (Mtr), Ile, Leu, Thr (tBu), tYR (tBu),Asn (Tmob) and Gln (Tmob). Tyr²⁷, Thr³² and Tyr³⁶ were D isomers. Toremove the side chain protecting group and separate the pepetide fromthe resin (PAL resin), TFA/thioanisol/ethanedithiol/anisol was used inmolar excess (10 ml/g). After deprotection of the final product, thepeptide was purified over a 2″×25 cm VYDAC 15-20 micron C₁₈ column usinga Waters model 600-E HPLC with 0.1% TFA and 60% acetonitrile in 0.1% TFAapplying a linear gradient over 45 minutes. The primary peak detected byUV absorbance at 215 nm was collected and repeatedly lyophilized. Thepurity of the end product, having the sequenceD-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH₂ (SEQ ID NO:1) (M.W.1336.57), was ≧95%.

Example 2

Synthesis of Additional NPY Analogs

The following compounds were synthesized in essentially the same manneras given in Example 1 above to yield the indicated compounds:

I^(Ac): Ac-D-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH₂  (SEQ IDNO:2) (M.W. 1378.62);

IIB:D-Asp-Pro-Lys-Ser-Pro-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH₂  (SEQID NO:3) (M.W. 1864.14);

IIB^(Ac):Ac-D-Asp-Pro-Lys-Ser-Pro-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH₂  (SEQID NO:4) (M.W. 1906.19);

III: D-Phe(NO₂)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(NO₂)-NH₂  (SEQID NO:5) (M.W. 1396.58);

III^(Ac):Ac-D-Phe(NO₂)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(NO₂)-NH₂  (SEQ IDNO:6(M.W. 1438.63);

IV: D-Phe(pF)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pF)-NH₂  (SEQ IDNO:7) (M.W. 1342.57);

 IV^(Ac):Ac-D-Phe(pF)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pF)-NH₂  (SEQ IDNO:8) (M.W. 1342.57);

V: D-Phe(pCl)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pCl)-NH₂  (SEQ IDNO:9) (M.W. 1359.02);

V^(Ac):Ac-D-Phe(pCl)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pCl)-NH₂  (SEQ IDNO:10) (M.W. 1401.07);

VI: D-Phg-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phg-NH₂  (SEQ ID NO:11)(M.W. 1306.54);

and

VI^(Ac): D-Phg-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phg-NH₂  (SEQ IDNO:12) (M.W. 1348.59).

Example 3

In Vivo Activity of NPY27-36 (D-Tyr^(27,36), D-Thr³²)

Male Sprague-Dawley rats obtained from Charles River Laboratories,Wilmington, Mass., and weighing 276-300 g, were group housed at 22° C.and kept on 12 hour light/dark cycle. Food and water were provided adlib.

Animals were anesthetized with sodium pentobarbital (65 mg/kg) and understerile conditions a one-inch incision was made in the fold of the leftleg to expose the femoral blood vessels. Two lengths of PE-50 tubingfilled with 10% heparin were inserted into the left femoral artery andleft femoral vein for measurement of blood pressure and for drugdelivery, respectively. The tubings were tunneled under the skin andexposed through the mid-scapular region. Animals were allowed at least24 hours recovery prior to experiments.

A force transducer (Spectramed Model P23XL, Grass Instruments, Quincy,Mass., USA), and tachograph (Model 7P44D, Grass Instruments) was usedfor recording of systolic and diastolic pressures and heart rate fromthe femoral artery catheter. Patency of catheters was verified byflushing with either saline or 10% heparin.

A dose of either 30, 100, 500, 800 or 1000 nM/kg (nanomoles per literper kilogram) of NPY27-36 (D-Tyr^(27,36), D-Thr³²) (prepared asdescribed in Example 1 above), or saline was delivered to the animal viathe catheter in the left femoral vein. Changes in systolic and diastolicpressures and heart rater were recorded from the catheter in the leftfemoral artery over a 10 minute time interval.

NPY27-36 (D-Tyr^(27,36), D-Thr³²) produced a dose-dependent decrease inmean arterial pressure and an increase in heart rate when givenintraveneously to the normotensive Sprague-Dawsley rats. Doses of 30 and100 nM/kg failed to produce changes that were significantly differentfrom saline treatment. When given in doses of 500, 800, and 1000 nM/Kg,however, significantly different decreases in mean arterial pressurewere seen ad is as compared to saline-treated controls. Further, dosesof 500 and 1000 nM/kg produced significantly different increases inheart rate as compared to saline controls.

The foregoing examples are illustrative of the present invention, andare not to be construed as limiting thereof. The invention is defined bythe following claims, with equivalents of the claims to be includedtherein.

That which is claimed is:
 1. A satiety inducing composition, comprisinga satiety induced amount of a modified Neuropeptide Y having satietyinducing activity and consisting of a fragment of 8 to 18 amino acids ofa Neuropeptide Y, which fragment comprises an amino acid segmentselected from the group consisting of amino acids 28 to 35 of aNeuropeptide Y, wherein D-Thr is substituted for Thr at position 32,pharmaceutically acceptable salts thereof, and mixtures thereof; and aphysiologically acceptable carrier.
 2. The composition of claim 1,wherein the modified Neuropeptide Y comprises 9 to 17 amino acids. 3.The composition of claim 2, wherein the modified Neuropeptide Ycomprises 10 to 16 amino acids.
 4. The composition of claim 3, whereinthe modified Neuropeptide Y comprises 15 amino acids.
 5. The compositionof claim 1, wherein the modified Neuropeptide Y is selected from thegroup consisting ofD-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH₂  (SEQ ID NO:1);D-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH₂  (SEQ ID NO:2);D-Asp-Pro-Lys-Ser-Pro-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH₂  (SEQID No:3);Ac-D-Asp-Pro-Lys-Ser-Pro-Tyr-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Tyr-NH2  (SEQID No:4);D-Phe(NO2)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(NO2)-NH2  (SEQ IDNO:5);Ac-D-Phe(NO2)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(NO2)-NH2  (SEQ IDNO:6); D-Phe(pF)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pF)-NH2  (SEQID NO:7);Ac-D-Phe(pF)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pF)-NH2  (SEQ IDNO:8); D-Phe(pCl)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pCl)-NH2  (SEQID NO:9);Ac-D-Phe(pCl)-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phe(pCl)-NH2  (SEQ IDNO:10); D-Phg-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phg-NH2  (SEQ IDNO:11); and D-Phg-Ile-Asn-Leu-Ile-D-Thr-Arg-Gln-Arg-D-Phg-NH2  (SEQ IDNO:12); wherein Ac represents acetyl, Phe(NO₂) represents NO₂substituted phenylalanine, Phe(pCl) represents phenylalanine substitutedby Cl on the phenylalanine ring, and Phe(pF) represents phenylalaninesubstituted by F on the phenylalanine.
 6. The composition of claim 5,wherein the modified Neuropeptide Y is freeze-dried or lyophilized. 7.The composition of claim 5, wherein the modified Neuropeptide Y is SEQ.ID NO: 1, a pharmaceutically acceptable salt thereof or mixturesthereof.
 8. The composition of claim 5, wherein the modifiedNeuropeptide Y is SEQ. ID NO: 2, a pharmaceutically acceptable saltthereof or mixtures thereof.
 9. The composition of claim 5, wherein themodified Neuropeptide Y is SEQ. ID NO: 3, a pharmaceutically acceptablesalt thereof or mixtures thereof.
 10. The composition of claim 5,wherein the modified Neuropeptide Y is SEQ. ID NO: 4, a pharmaceuticallyacceptable salt thereof or mixtures thereof.
 11. The composition ofclaim 5, wherein the modified Neuropeptide Y is SEQ. ID NO: 5, apharmaceutically acceptable salt thereof or mixtures thereof.
 12. Thecomposition of claim 5, wherein the modified Neuropeptide Y is SEQ. IDNO: 6, a pharmaceutically acceptable salt thereof or mixtures thereof.13. The composition of claim 5, wherein the modified Neuropeptide Y isSEQ. ID NO: 7, a pharmaceutically acceptable salt thereof or mixturesthereof.
 14. The composition of claim 5, wherein the modifiedNeuropeptide Y is SEQ. ID NO: 8, a pharmaceutically acceptable saltthereof or mixtures thereof.
 15. The composition of claim 5, wherein themodified Neuropeptide Y is SEQ. ID NO: 9, a pharmaceutically acceptablesalt thereof or mixtures thereof.
 16. The composition of claim 5,wherein the modified Neuropeptide Y is SEQ. ID NO: 10, apharmaceutically acceptable salt thereof or mixtures thereof.
 17. Thecomposition of claim 5, wherein the modified Neuropeptide Y is SEQ. IDNO: 11, a pharmaceutically acceptable salt thereof or mixtures thereof.18. The composition of claim 5, wherein the modified Neuropeptide Y isSEQ. ID NO: 12, a pharmaceutically acceptable salt thereof or mixturesthereof.
 19. The composition of claim 1, wherein the modifiedNeuropeptide Y is operatively linked to a Neuropeptide Y-unrelated aminoacid segment, a pharmaceutically acceptable salt thereof or mixturesthereof.
 20. The composition of claim 1, wherein the carrier is apharmaceutically acceptable carrier.
 21. The composition of claim 1,comprising about 0.5 to about 99% of the modified Neuropeptide Y. 22.The composition of claim 1, wherein the carrier is selected from thegroup consisting of solid and liquid carriers.
 23. The composition ofclaim 1, which further comprises an agent selected from the groupconsisting of other therapeutic agents, flavorings, lubricants,suspending and thickening agents, binders, inert diluents, surfaceactive agents, dispersants, antioxidants, buffers, bacteriostats andsolutes to attain isotonicity.
 24. The composition of claim 23,comprising a therapeutic agent that is a tubercular agent.
 25. Thecomposition of claim 1, which is in the form of a formulation selectedfrom the group consisting of inhalable, oral, rectal, topical,parenteral, and transdermal formulations.
 26. The formulation of claim25, which is selected from the group consisting of buccal, sublingual,dermal, intraocular, subcutaneous, intradermal, intramuscular,intravenous, iontophoretic, intraarticular, and transdermalformulations.
 27. The formulation of claim 25, which is in a formselected from the group consisting of capsules, cachets, pastilles,lozenges, powder, granules, solution, suspension, emulsion and tablets.28. The formulation of claim 27, which comprises a suspension orsolution in an aqueous or non-aqueous liquid or an oil-in-water orwater-in-oil emulsion.
 29. The formulation of claim 27, which is in theform of a capsule.
 30. The formulation of claim 25, which is an oralformulation.
 31. The oral formulation of claim 30, which comprises asolution or suspension selected from the group consisting of aqueous andnon-aqueous liquid solutions and suspensions.
 32. The oral formulationof claim 30, which comprises an emulsion selected from the groupconsisting of oil-in-water and water-in-oil emulsions.
 33. The oralformulation of claim 30, which further comprises an enteric coating. 34.The formulation of claim 25, which comprises a buccal or sub-lingualformulation selected from the group consisting of lozenges furthercomprising a flavoring agent selected from the group consisting ofsucrose, acacia and tragacanth; and pastilles further comprising aninert base selected from the group consisting of gelatin, glycerin,sucrose and acacia.
 35. The formulation of claim 25, which comprises aparenteral formulation.
 36. The parenteral formulation of claim 35,which comprises a solution, suspension or emulsion.
 37. The parenteralformulation of claim 35, which is an injectable formulation.
 38. Theinjectable formulation of claim 37, which is selected from the groupconsisting of injectable solutions or suspensions, and which may furthercomprise an agent selected from the group consisting of antioxidants,buffers, bacteriostatic agents and solutes which render the solution orsuspension isotonic with the blood of a recipient.
 39. The injectableformulation of claim 38, wherein the solutions and suspensions areselected from the group consisting of sterile aqueous and non-aqueousinjection solutions and suspensions, which may further comprisesuspending agents and thickening agents.
 40. The formulation of claim25, which is a topical formulation selected from the group consisting ofointments, creams, lotions, pastes, gels, sprays, aerosols and oils; andmay further comprise a carrier selected from the group consisting ofvaseline, lanoline, polyethylene glycols, alcohols and trans-dermalenhancers.
 41. The formulation of claim 25, which is a transdermalformulation.
 42. The transdermal formulation of claim 41, which iscomprised in a transdermal device.
 43. The transdermal formulation ofclaim 41, which comprises an iontophoretic formulation selected from thegroup consisting of iontophoretic solutions and suspensions, and whichmay further comprise a buffer.
 44. The transdermal formulation of claim42, wherein the transdermal device is an iontophoretic device furthercomprising means for iontophoretic delivery.
 45. The composition ofclaim 23, which is in the form of a sub-lingual formulation, furthercomprising a flavoring and inert diluent selected from the groupconsisting of sucrose, acacia, tragacanth, gelatin and glycerin.
 46. Theformulation of claim 25, which is a rectal formulation.
 47. Theformulation of claim 25, which is an inhalable formulation.
 48. Theformulation of claim 25, which is an intraocular formulation.
 49. Amethod of inducing satiety, comprising administering to a subject inneed of treatment a satiety inducing amount of the composition ofclaim
 1. 50. The method of claim 49, wherein the composition isadministered parenterally.
 51. The method of claim 49, wherein thecomposition is administered orally, intraocularly, or buccally.
 52. Themethod of claim 49, wherein the composition is administered dermally,transdermally, intradermally, intraarticularly, or iontophoretically.53. The method of claim 49, wherein the composition is administeredtopically.
 54. The method of claim 49, wherein the composition isadministered transdermally.
 55. The method of claim 49, wherein thecomposition is administered sub-lingually.
 56. The method of claim 49,wherein the composition is administered rectally.
 57. The method ofclaim 49, wherein the composition is administered by means of atransdermal device comprising a patch.
 58. The method of claim 49, whichis a prophylactic method.
 59. The method of claim 49, which is atherapeutic method.
 60. The method of claim 49, wherein the compositionis administered in an amount of about 400 to about 4000 nmole/kg bodyweight.
 61. The method of claim 49, wherein the subject is human. 62.The method of claim 49, wherein the subject is an animal.
 63. A methodof treating a disease or condition associated with low, or lack of,satiety, comprising administering to a subject in need of such treatmentthe method of claim 49, wherein the composition comprises atherapeutically effective amount of the modified Neuropeptide.
 64. Themethod of claim 63, wherein the composition is administered rectally.65. The method of claim 63, wherein the composition is administereddermally, parenterally, transdermally or intraarticularly.
 66. Themethod of claim 63, wherein the composition is administered byinhalation.
 67. The method of claim 63, wherein the composition isadministered intraocularly.
 68. The method of claim 63, wherein thecomposition is administered sublingually or orally.
 69. The method ofclaim 63, wherein the composition is administered buccally.
 70. Themethod of claim 63, wherein the composition is administeredsubcutaneously, intradermally, intramuscularly, intravenously orintraarticularly.
 71. The method of claim 63, wherein the composition isadministered dermally.
 72. The method of claim 63, wherein thecomposition is administered by means of a patch.
 73. The method of claim63, wherein the composition is administered by iontophoresis.